Answers to common and uncommon questions that come up during the course of ICU rounds at the University of Virginia Medical Center. Curated and developed by Jordan Hackworth, M.D.

Thursday, September 16, 2010

SICU Rounds Report - Sept 9th, 2010

Bumetanide Side effects. Basically 3 things to consider. First is an untoward effect from the diuresis. We talk about these every day during rounds, they are mainly: hypokalemia, 'contraction' metabolic alkalosis (which is common), hypotension, rising BUN/Cr, and hyponatremia. Next, allergic reactions are possible. Like furosemide, HCTZ and celebrex, bumetanide is a sulfonamide. However, most allergic reactions to 'sulfa' drugs are from sulfonamide anti-microbials (e.g. bactrim). There appears to be little, if any, cross reactivity. Unless the 'sulfa allergy' is steven's johnson syndrome there is no contraindication to using these drugs in patients who are allergic to the antimicrobials. Finally, these drugs reliably cause ototoxicity, in a dose dependent fashion. Most of the literature is with furosemide. Typically, this is reported when high doses (>200 mg/day) are used over many days. The risk of ICU induced-deafness is even higher when used in patients with renal failure or/and comcominant aminogylcosides. It can be minimized with continuous, rather than bolus, dosing of diuretics. It appears to be reversible if caught soon enough. Finally, there is animal data from at least 3 trials to suggest the bumetanide is less likely to poison ears, but this is unclear in humans.Strom, BL, Schinnar, R, Apter, AJ, Margolis, DJ. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003; 349:1628.
Göttl KH, Roesch A, Klinke R. Quantitative evaluation of ototoxic side effects of furosemide, piretanide, bumetanide, azosemide, and ozolinone in the cat a new approach to the problem of ototoxicity. Naunyn Schmiedebergs Arch Pharmacol. 1985;331 (2-3):275-282.

PPI vs H2 Blocker. Ulcer prophylaxis is recommended for intubated patients, those with history of PUD, those who are coagulopathic or in those with at least two minor risk factors (sepsis, ICU admission lasting >1 week, occult GI bleeds and steroid therapy). Which drug should you choose? Sulcralfate and antacids work, but not quite as well as H2 or PPIs. In a recent meta-analysis, no difference was seen between the latter two on any outcome (bleeds, PNA, death) so it probably doesn't matter. Because IV is equivalent to PO, the cheapest feasible form should be chosen. For years, there has been concern that these drugs may increase the risk of nosocomial PNA (which may mean in the future we'll be switching back to sulcralfate, which doesn't). This is based on one prospective paper and some retrospective analyses. But until that link becomes more robust, the recommendation is for PPI or H2 blockers.Lin, PC, Chang, CH, Hsu, PI, et al. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med 2010; 38:1197.
Driks, MR, Craven, DE, Celli, BR, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. N Engl J Med 1987; 317:1376.
Cook, DJ, Reeve, BK, Guyatt, GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996; 275:308.

From Patrick:MELD Scoring and mortality: The Model for End-Stage Liver Disease (MELD) is a scoring system originally developed by the GI-Hepatology dept at Mayo clinic to predict mortality in patients who recently underwent an elective TIPS procedure (1), but quickly found utility in predicting need for liver transplant and is currently used by the United Network for Organ Sharing (UNOS) as a replacement to the older Child-Pugh scoring system. The MELD score is calculated as such (2): 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43 x etiology (0: if alcoholic or cirrhotic, 1: if otherwise)
Scoring Notes:
- If pt has been dialysed twice within the last 7 days, a creatinine value of 4.0mg/dl is used.
- Any value less than 1 is given a value of 1.0 (to prevent negative values w/natural log)
- Some centers use an "etiology" value of 1 regardless.
- An integrated MELD model (iMELD, incorporating serum sodium and age), has better long term (12 month) mortality prediction (3).
Studies have consistently shown a direct relationship between increasing MELD score and short-term mortality rate in patients with end-stage liver disease. In one study of 3437 adults with chronic liver disease, mortality rates were as follows (4):

MELD score: 3-month Mortality:

<9 1.9%
10-19 6.0%
20-30 19.6%
30-40 52.6%
>40 71.3%

Clearly there is an exponential relationship between increasing MELD score and the 3-month mortality rate in patients with chronic liver disease, and thus the MELD score also serves as a good tool when considering proper allocation of liver donations. However, the MELD can also be used preoperatively to predict nontransplant surgical mortality in cirrhotic patients. One study conducted at the magnificent, absolutely spectacular and awesome University of Virginia suggested this general rule of thumb (5):

From Max:Gastrointestinal Amyloidosis. Amyloidosis is a clinical disorder caused by extracellular and or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. Systemic amyloidosis is characterized by the extracellular deposition of protein in an abnormal fibrillar form. Among patients with systemic amyloidosis, histological involvement of the gastrointestinal tract is very common but is often subclinical. Gastrointestinal disease is present in as many as 60% of patients with reactive amyloidosis and results from either mucosal infiltration or neuromuscular infiltration. Extrinsic autonomic neuropathy also affects gut function. Patients with symptomatic gastrointestinal amyloidosis usually present with one of four syndromes:

○ Chronic intestinal dysmotility in which dilatation of the intestine is more likely in the myopathic, infiltrative stage of the disease. These patients have stasis syndromes such as dysphagia, gastroparesis, constipation, or chronic intestinal pseudo-obstruction.

○ Malabsorption due to mucosal infiltration or bacterial overgrowth.

○ Protein-losing gastroenteropathy.

Amyloidosis & Small bowel diverticuli. Amyloidosis with small bowel diverticula and/or perforation is very rare. However, reports have suggested a poor prognosis. The reported incidence in the general population is less than 0.1%. The etiology and pathogenesis of small intestinal diverticula remain poorly understood. Diverticula can be congenital, occurring in young patients, or acquired, occurring in elderly patients. Unlike these diverticula, the amyloid-associated diverticula can be located not only on the mesenteric side but also on the antimesenteric side. The pathology of digestive alterations is complex, and the organic infiltration by amyloid substance is localized in the wall of blood vessels, producing deficits of function and several alterations in which ischemia plays an important role. As the process continues, the wall of the blood vessels becomes thicker and the lumen becomes occluded. The blood supply is progressively impaired, which leads to ischemia, infarction, and the wall of the small bowel become thinner and weaker, as seen in our patient. Bleeding, diverticula, and finally perforation are complications of the amyloidosis.

Gastrointestinal bleeding is not uncommonly found in the patients with amyloidosis. Ulceration can be asymptomatic or may be associated with bleedings. Bleeding can be chronic or intermittent. Sometimes the lesion can be identified as an amyloid "tumor" with superficial ulceration. Often either no lesion is found at laparotomy or at autopsy, or diffuse bleeding is encountered. The relationship between H. pylori and amyloidosis in the formation of ulcer is unknown. In cases of intestinal obstruction, especially in order individuals with perforation, amyloidosis should be considered in the differential diagnosis.Camilleri M. Gastrointestinal amyloidosis. UpToDate 2010.
Holmes et al. amyloidosis, overview. Emedicine 2009
Kuang et al.Gastrointestinal Amyloidosis with Ulceration, Hemorrhage, Small bowel Diverticula, and Perforation. Digestive Diseases and Sciences 2003. Vol. 48, No. 10 pp. 2023–2026
Sattianayagam et al. Systemic amyloidosis and the gastrointestinal Tract. Nature Reviews Gastroenterology & Hepatology 2009. Volume 6. 608-617
Willekens et al. Gastrointestinal amyloidosis presenting as enterocolitis on abdominal CT scan. Radiology Case. 2009 Oct; 3(10):11-14

From Chris:Adult Enteral Solutions at UVa. There are dozens of enteral feeding solutions on the market. Lots are designed for specific clinical indications. But, most have no data to back up their claims (eg TraumaCal, a feeding formula with high levels of vitamins that is supposed to speed wound healing). UVA carries 6 enteral solutions that are used fairly commonly in adults. Unless otherwise noted all are hyperosmolar and gluten and lactose free. Standard formulas are 1kCal per ml.

Nepro: This is optimized for people with ESRD whether they are dialysis dependent or not. It has low electrolyte levels and a moderate protein content.

Two Cal HN w/ FOS: This is a highly concentrated solution for patients that must be fluid restricted (CHF, etc).

Osmolite: This is the standard selection for people who need an isotonic solution for fluid management problems (liver failure, etc.)

Jevity: An isotonic formula similar to Osmolite but with additional fiber. It's a common choice for the elderly. There is a 1.5 kCal variety for people who want lower feeding volumes or shorter tube feeding times.

Promote: This is our default solution. It is considered nutritionally complete. But, the dietitians often add additional protein based on a patient's calculated protein need. It also comes in a fiber fortified variety

Impact: This is a fairly standard formula with a higher level of fiber and protein. It is billed as immune enhancing and designed for critical care use. But, the data for this is uncertain. It's use seems to be based mostly on personal preference.